Methylation levels in the GRIN2B promoter region are associated with bipolar disorder and its anxiety and insomnia symptoms

This study investigated the potential role of promoter-region DNA methylation in <i>GRIN2B</i> in bipolar disorder (BD) and its association with anxiety and insomnia symptoms among patients with BD. The DNA methylation levels in the <i>GRIN2B</i> promoter region were quantified using MassARRAY technology in peripheral blood samples from 31 patients with BD and 32 healthy controls. To assess associations, binary logistic regression and partial correlation analyses were performed to examine potential links between <i>GRIN2B</i> methylation, BD diagnosis and symptom severity. The exploratory analysis revealed six differentially methylated CpG sites between groups, four of which exhibited hypermethylation in patients with BD compared with the controls. Significant positive correlations were observed between Hamilton Anxiety Rating Scale scores and CpG9 methylation (r=0.408, P=0.038), as well as between Pittsburgh Sleep Quality Index scores and CpG8 methylation (r=0.419, P=0.033). These findings provide preliminary evidence supporting an association between <i>GRIN2B</i> methylation levels and BD, as well as related clinical symptoms. However, given the small sample size and the exploratory nature of this study, these results should be interpreted with caution. Further replication in larger, longitudinal cohorts is warranted to confirm these observations and evaluate their clinical implications.